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Objective: To evaluate the efficacy and acceptability of a self-help program for mild-to-moderate depression that combined treatment booklets and telephone calls to a computer-aided Interactive Voice Response (IVR) system., Method: In an open trial, 41 patients from Boston, Massachusetts; Madison, Wisconsin; and London, England, used COPE, a 12-week self-help system for depression. COPE consisted of an introductory videotape and 9 booklets accompanied by 11 telephone calls to an IVR system that made self-help recommendations to patients based on information they entered., Results: All 41 patients successfully completed the self-assessment in the booklets and telephone calls; 28 (68%) also completed the 12-week self-help program. Hamilton Rating Scale for Depression (HAM-D) and Work and Social Adjustment scores improved significantly (41% and 42% mean reduction in the intent-to-treat sample, respectively, p < .001). Eighteen (64%) of the 28 completers were considered responders on the basis of > or = 50% reduction in their HAM-D scores. There was a higher percentage of completers in the pooled U.S. sites (82% vs. 43%), and U.S. completers improved more than those in the United Kingdom (73% vs. 43% were responders). Most (68%) of the calls were made outside usual office hours, Monday-Friday, 9:00 a.m. to 5:00 p.m. Expectation of effectiveness and time spent making COPE calls (more treatment modules) correlated positively with improvement over 12 weeks. Mean call length for completers was 14 minutes., Conclusion: A self-help system comprised of a computer-aided telephone system and a series of booklets was used successfully by people with mild-to-moderate depression. These preliminary results are encouraging for people who cannot otherwise access ongoing, in-person therapy.